Metabolic pre-conditioning of cultured cells in physiological levels of insulin: Generating resistance to the lipid-accumulating effects of plasma in hepatocytes

Christina Chan, François Berthiaume, Junji Washizu, Mehmet Toner, Martin L. Yarmush

Research output: Research - peer-reviewArticle

  • 26 Citations

Abstract

Understanding the regulation of hepatocyte lipid metabolism is important for several biotechnological applications involving liver cells. During exposure of hepatocytes to plasma, as is the case in extracorporeal bioartificial liver assist devices, it has been reported that hepatic-specific functions, e.g., albumin and urea synthesis and diazepam removal, are dramatically compromised and hepatocytes progressively accumulate cytoplasmic lipid droplets. We hypothesized that the composition of hepatocyte culture medium significantly affects lipid metabolism during subsequent plasma exposure. Rat hepatocytes were cultured in medium containing either physiological (50 μU/mL) or supraphysiological (500 mU/mL) insulin levels for 1 week and then exposed to human plasma supplemented with or without amino acids. We found that insulin's anabolic effects, such as stimulation of triglyceride storage, were carried over from the pre-conditioning to the plasma exposure period. While hepatocytes cultured in high insulin medium accumulated large quantities of triglycerides during subsequent plasma exposure, culture in low insulin medium largely prevented lipid accumulation. Urea and albumin secretion, as well as the ammonia removal rate, were largely unaffected by insulin but increased with amino acid supplementation. Thus, hepatocyte metabolism during plasma exposure can be modulated by medium pre-conditioning and supplements added to plasma.

LanguageEnglish (US)
Pages753-760
Number of pages8
JournalBiotechnology and Bioengineering
Volume78
Issue number7
DOIs
StatePublished - Jun 30 2002
Externally publishedYes

Profile

Cells
Insulin
Lipids
Plasmas
Hepatocytes
Insulin Resistance
Cultured Cells
Liver
Urea
Albumins
Triglycerides
Amino Acids
Lipid Metabolism
Amino acids
Plasma (human)
Anabolic Agents
Diazepam
Ammonia
Metabolism
Culture Media

Keywords

  • Bioartificial liver
  • Hepato-specific function
  • Hepatocytes
  • Insulin
  • Lipid accumulation
  • Plasma
  • Pre-conditioning

ASJC Scopus subject areas

  • Biotechnology
  • Microbiology

Cite this

Metabolic pre-conditioning of cultured cells in physiological levels of insulin : Generating resistance to the lipid-accumulating effects of plasma in hepatocytes. / Chan, Christina; Berthiaume, François; Washizu, Junji; Toner, Mehmet; Yarmush, Martin L.

In: Biotechnology and Bioengineering, Vol. 78, No. 7, 30.06.2002, p. 753-760.

Research output: Research - peer-reviewArticle

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